This invention relates to zinc supplements for oral use. More particularly, this invention relates to compositions containing a zinc compound which, when taken orally, is palatable without undesirable aftertaste. These compositions include, in addition to the zinc compound, a base material and a select amino acid.
The value of nutritional supplements of the element zinc is well established. Although zinc has been known to be essential for plant growth for more than a century, its essentiality for the normal growth of animals was reported in 1934 and for man in 1963. Hypogonadism in males, skin changes, poor appetite, and mental lethargy are but some of the observable effects related to zinc deficiency in man. Carbonic anhydrase was the first zinc metalloenzyme, discovered in the 1930's. Today, approximately 70 enzymes, many of them essential to human well being, have been found to contain zinc, and the evidence is strong that zinc is required for many (if not all) of these enzymes to express their activity. Several enzymes required for nucleic acid metabolism have been shown to require zinc. In this group are ribonucleic acid (RNA) and deoxyribonucleic acid (DNA) polymerases, deoxythymidine kinase, and reverse transcriptase. It has been shown experimentally that the activity of deoxythymidine kinase in rapidly regenerating connective tissue decreases as early as six days after animals are placed on a zinc-deficient diet. This metabolic defect resulting from nutritional zinc deficiency is an indication of the fundamental importance of zinc for cell division and protein synthesis.
Until recently, zinc deficiency in man was considered unlikely because of the widespread availability of zinc in nature. However, recent evidence suggests that nutritional zinc deficiency may be common among the people of many developing countries where they subsist on high cereal protein diets. Only recently has it been recognized that the phytate content of such diets severely restricts zinc availability, which translates nutritionally to markedly depressed zinc absorption in man under many practical circumstances. Marginal zinc deficiency may be widespread even in the United States because of self-imposed dietary restrictions, use of alcohol and cereal proteins, and the increasing use of refined foods which decrease the intake of trace elements. As meat is a major dietary source of zinc, vegetarians who consume cereals as a major source of protein may be in double jeopardy of zinc deficiency.
Therapeutically, zinc has a vital role in certain diseased or debilitated states. Zinc therapy is life saving in acrodermatitis enteropathica, a genetic disease caused by an autosomal recessive trait, which, although rare, had an extremely high mortality rate until it was discovered in 1973 that chronic administration or oral zinc salts was not only life saving but capable of lifetime control of the disease. Zinc supplementation markedly improves wound healing in zinc-deficient individuals. Zinc deficiency is an important feature of many cases of sickle cell anemia characterized by growth retardation and hypogonadism, and zinc appears to have a pharmacological antisickling effect. Zinc has also been shown to be beneficial in the relief of acute inflammatory conditions associated with rheumatoid arthritis.
The safety of zinc supplements in excess of the amounts found in a normal diet is well documented. Although excessive zinc produces toxic symptoms, such symptoms are rare. An acute dose of 2 g of zinc sulfate has been recommended as an emetic. Except for extremely large doses, zinc is non-toxic.
Until the present time, the more or less water-soluble zinc compounds such as the sulfate, chloride, acetate, gluconate, and the like, have been formulated as solid tablets or enclosed in gelatin capsules which are swallowed whole. Accordingly, the taste buds and other taste apparatus in the mouth and throat were not affected. These formulations generally dissolve in the gastric juice of the stomach and release zinc ion to be absorbed into the system via the stomach and intestines. It has only recently been found by a serendipitous observation of G. A. Eby, D. R. Davis, and W. W. Halcomb as reported in "Reduction in Duration of Common Colds by Zinc Gluconate Lozenges in a Double Blind Study," Antimicrobial Agents & Chemotherapy, 1984, 25(1), pp. 20-24; that when modest quantities of zinc are slowly ingested by mouth so that the interior surfaces of the mouth and throat are intermittently bathed in a solution of ionic zinc, both the time course and the severity of the symptoms of the common cold are remarkably altered in a favorable way. Their double blind clinical study in sixty-five humans has shown that allowing a tablet containing about 23 mg of elemental zinc, such as zinc gluconate, to slowly dissolve in the mouth once every two hours during 12 to 16 hours a day (the waking hours) reduced the duration of colds from 10.8 days in the untreated group to 3.9 days in the zinc-treated group; and at every time after about one day, the zinc-treated patients had a great reduction in cold symptoms compared to the patients who did not receive zinc. While the reported observations are highly significant both from the point of view of statistical validity and of the importance of these observations to public health, the authors stated repeatedly in their paper that the disagreeable taste of the zinc gluconate tablets was a serious problem. Many patients receiving zinc gluconate discontinued the treatment on the first day "due to objection to treatment." The authors stated that "the zinc gluconate lozenges [tablets] we used caused a unexpected unpalatability and distortion of taste in many subjects . . . " and mentioned "the somewhat bitter aftertaste which some people report for zinc gluconate." Furthermore, "unpalatable taste," "distortion of taste," and "mouth irritation" were common objections.
Accordingly, in order to take advantage of the important effect of zinc upon the common cold it is necessary to develop a formulation or formulations of pharmaceutically acceptable zinc salts which are palatable enough to be taken with the frequency necessary to suppress the symptoms of the common cold.
Another reason for developing zinc formulations having acceptable taste is to permit an increased oral dosage. Thus, it has been found that the ingestion of zinc as tablets or capsules which pass directly to the stomach before disintegrating is ineffective for providing a zinc supplement for certain applications, including the control of cold symptoms.
It has been found, however, that while minimal improvements in the taste of zinc gluconate, zinc acetate, zinc citrate, and the like salts can be achieved by physically mixing these salts with a candy or syrup base and adding a flavoring agent such as fruit flavor concentrate, the products so obtained retain the objectionable taste characteristics of the unformulated salts to an undesirable and unacceptable degree.